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C 反应蛋白水平在系统性红斑狼疮中受干扰素基因特征和 CRP 基因多态性 rs1205 调节。

C-Reactive Protein Levels in Systemic Lupus Erythematosus Are Modulated by the Interferon Gene Signature and CRP Gene Polymorphism rs1205.

机构信息

Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linköping University, Linköping, Sweden.

Department of Clinical Sciences Lund, Division of Rheumatology, Lund University, Lund, Sweden.

出版信息

Front Immunol. 2021 Jan 28;11:622326. doi: 10.3389/fimmu.2020.622326. eCollection 2020.

Abstract

OBJECTIVES

Patients with systemic lupus erythematosus (SLE) often display modest elevations of C-reactive protein (CRP) despite raised disease activity and increased interleukin (IL-) 6. We asked to what extent IL-6 levels, the CRP polymorphism rs1205, and the type I interferon (IFN) gene signature affects the basal CRP levels in patients with SLE during a quiescent phase of the disease.

METHODS

CRP and IL-6 were analyzed in plasma from 57 patients meeting established classification criteria for SLE. The CRP polymorphism rs1205 was assessed and gene expression analyzed including four type I IFN-regulated genes (IGS).

RESULTS

CRP was increased in patients with detectable IL-6 levels (p=0.001) and decreased among IGS-positive subjects (p=0.033). A multiple linear regression model revealed IL-6 to have a positive association with CRP levels, whereas both IGS-positivity and CRP genotype (rs1205) AA/GA were negatively associated with CRP-levels.

CONCLUSION

Our data offer an explanation to the modest CRP levels seen in viral infections and IFN-α driven autoimmunity and corroborate prior observations showing an IFN-α dependent downregulation of CRP. The latter observation, together with the fact that the CRP-lowering polymorphism rs1205 is overrepresented in human SLE, could explain low basal CRP and inadequate CRP-responses among patients with active SLE.

摘要

目的

尽管系统性红斑狼疮(SLE)患者的疾病活动度增加且白介素(IL)-6 水平升高,但仍有部分患者的 C 反应蛋白(CRP)水平仅略有升高。我们想知道在疾病静止期,IL-6 水平、CRP 多态性 rs1205 以及 I 型干扰素(IFN)基因特征在多大程度上影响 SLE 患者的基础 CRP 水平。

方法

分析 57 例符合 SLE 既定分类标准的患者的血浆 CRP 和 IL-6 水平。评估 CRP 多态性 rs1205,并分析包括四个 I 型 IFN 调节基因(IGS)在内的基因表达。

结果

可检测到 IL-6 水平的患者 CRP 升高(p=0.001),而 IGS 阳性患者的 CRP 降低(p=0.033)。多元线性回归模型显示,IL-6 与 CRP 水平呈正相关,而 IGS 阳性和 CRP 基因型(rs1205)AA/GA 与 CRP 水平呈负相关。

结论

我们的数据为病毒感染和 IFN-α驱动的自身免疫中观察到的适度 CRP 水平提供了一种解释,并证实了先前观察到的 IFN-α 依赖性 CRP 下调。后一种观察结果,加上 CRP 降低的 rs1205 多态性在人类 SLE 中过度表达,可解释活动性 SLE 患者的基础 CRP 水平低和 CRP 反应不足。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb87/7876312/4f8da25466db/fimmu-11-622326-g001.jpg

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